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71.
Fabrice Smieliauskas Hari Sharma Connor Hurley Jonas A. de Souza Ya‐Chen Tina Shih 《Health economics》2018,27(1):e55-e70
Access to cancer drugs used off‐label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off‐label use of cancer drugs cause higher rates of off‐label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off‐label coverage laws. We studied trends in off‐label use of drugs, distinguishing between appropriate and inappropriate off‐label use according to drug compendia, and estimated difference‐in‐difference regressions of the effect of state laws on off‐label use. We estimate 41% of utilization was off‐label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off‐label use over time. We also find no discernable effect of state laws mandating coverage of off‐label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off‐label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off‐label use. 相似文献
72.
Emily A. Hurley Steven A. Harvey Peter J. Winch Mariam Keita Debra L. Roter Seydou Doumbia 《Journal of health communication》2018,23(2):129-143
Mounting evidence in sub-Saharan Africa suggests poor patient-provider communication (PPC) negatively impacts patient engagement (retention in care and adherence to medication) in antiretroviral therapy (ART) programs. In Bamako, Mali, where 36% of ART patients are lost to follow-up within 12 months of initiating treatment, we aimed to define features of positive PPC according to patient values and explore the mechanisms by which these features may sustain engagement and re-engagement according to patient and provider experiences. We conducted 33 in-depth interviews and 7 focus groups with 69 patients and 17 providers in five ART clinics. Regarding sustaining engagement, participants highlighted “establishing rapport” as a foundational feature of effective PPC, but also described how “responding to emotional needs”, “eliciting patient conflicts and perspective” and “partnering to mitigate conflicts” functioned to address barriers to engagement and increase connectedness to care. Patients who had disengaged felt that “communicating reacceptance” may have prompted them re-engage sooner and that tailored “partnering to mitigate conflicts” would be more effective in sustaining re-engagement than the standard adherence education providers typically offer. Optimizing provider skills related to these key PPC features may help maximize ART patient engagement, ultimately improving health outcomes and decreasing HIV transmission in sub-Saharan Africa. 相似文献
73.
Mariana T. Garcia Priscila M. Sato Angela C. B. Trude Thomas Eckmann Elizabeth T. Anderson Steeves Kristen M. Hurley 《Ecology of food and nutrition》2018,57(1):13-31
This study aimed to assess the factors associated with home meal preparation (HMP) and fast-food sources use (FFS) frequencies of low-income African-American adults and their healthy food beliefs and attitudes, food-related psychosocial factors, food acquisition patterns, food sources use, and BMI. We used cross-sectional data from 295 adults living in Baltimore, USA. HMP was inversely associated with FFS, which had lower odds of HMP ≥1 time/day and higher BMI scores. HMP was positively associated with positive beliefs and self-efficacy toward healthy foods, getting food from healthier food sources, and lower FFS. Higher odds of HMP ≥1 time/day were associated with getting food from farmers’ market and supermarkets or grocery stores. FFS had an inverse association with positive beliefs and self-efficacy toward healthy foods, and a positive association with less healthy food acquisition scores. Higher odds of FFS ≥1 time/week were associated with getting food from corner stores, sit-down restaurants, and convenience stores. 相似文献
74.
Linsley P Hurley J 《Nursing standard (Royal College of Nursing (Great Britain) : 1987)》2007,21(37):41-44
Nursing faces new opportunities and challenges as part of the government's initiative to introduce Payment by Results. These opportunities arise from increasing demands to work effectively in an environment of intensive customer demand and expectation. The challenge for all nurses is to continue to deliver quality health care while keeping pace with changes to services and organisational responsiveness. It is important that nurses and other health professionals ensure that the needs of patients are not compromised in the pursuit of financial reward and that systems of work are improved as part of this initiative. 相似文献
75.
Hurley AC Bane A Fotakis S Duffy ME Sevigny A Poon EG Gandhi TK 《The Journal of nursing administration》2007,37(7-8):343-349
Efforts to promote safe care prompted the development point-of-care technology, but successful adoption requires acceptance by nursing staff. To assess the satisfaction of nurses who use point-of-care technology that integrates nurse scanning of bar-coded medications with the patient's electronic medication administration record, the authors examined nurses' satisfaction with barcode/electronic medication administration record before and after introduction in an academic medical center. 相似文献
76.
77.
Francis W. Hunter Jagdish K. Jaiswal Daniel G. Hurley H.D. Sarath Liyanage Sarah P. McManaway Yongchuan Gu Susan Richter Jingli Wang Moana Tercel Cristin G. Print William R. Wilson Frederik B. Pruijn 《Biochemical pharmacology》2014
The nitro-chloromethylbenzindoline prodrug SN29428 has been rationally designed to target tumour hypoxia. SN29428 is metabolised to a DNA minor groove alkylator via oxygen-sensitive reductive activation initiated by unknown one-electron reductases. The present study sought to identify reductases capable of activating SN29428 in tumours. Expression of candidate reductases in cell lines was modulated using forced expression and, for P450 (cytochrome) oxidoreductase (POR), by zinc finger nuclease-mediated gene knockout. Affymetrix microarray mRNA expression of flavoreductases was correlated with SN29428 activation in a panel of 23 cancer cell lines. Reductive activation and cytotoxicity of prodrugs were measured using mass spectrometry and antiproliferative assays, respectively. SN29428 activation under hypoxia was strongly attenuated by the pan-flavoprotein inhibitor diphenyliodonium, but less so by knockout of POR suggesting other flavoreductases contribute. Forced expression of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), as well as POR, increased activation of SN29428 in hypoxic HCT 116 cells. SN29428 activation strongly correlated with expression of POR and also FAD-dependent oxidoreductase domain containing 2 (FOXRED2), in cancer cell lines. This association persisted after removing the effect of POR enzyme activity using first-order partial correlation. Forced expression of FOXRED2 increased SN29428 activation and cytotoxicity in hypoxic HEK293 cells and also increased activation of hypoxia-targeted prodrugs PR-104A, tirapazamine and SN30000, and increased cytotoxicity of the clinical-stage prodrug TH-302. Thus this study has identified three flavoreductases capable of enzymatically activating SN29428, one of which (FOXRED2) has not previously been implicated in xenobiotic metabolism. These results will inform future development of biomarkers predictive of SN29428 sensitivity. 相似文献
78.
Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase 总被引:17,自引:0,他引:17
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Chen CK Burns ME Spencer M Niemi GA Chen J Hurley JB Baylor DA Simon MI 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(7):3718-3722
Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the single-photon response to become larger and longer lasting than normal. These results demonstrate that RK is required for normal rhodopsin deactivation. When the photon responses of RK-/- rods did finally turn off, they did so abruptly and stochastically, revealing a first-order backup mechanism for rhodopsin deactivation. The rod outer segments of RK-/- mice raised in 12-hr cyclic illumination were 50% shorter than those of normal (RK+/+) rods or rods from RK-/- mice raised in constant darkness. One day of constant light caused the rods in the RK-/- mouse retina to undergo apoptotic degeneration. Mice lacking RK provide a valuable model for the study of Oguchi disease, a human RK deficiency that causes congenital stationary night blindness. 相似文献
79.
A behavioral screen for isolating zebrafish mutants with visual system defects. 总被引:6,自引:0,他引:6
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S E Brockerhoff J B Hurley U Janssen-Bienhold S C Neuhauss W Driever J E Dowling 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(23):10545-10549
Optokinetic and phototactic behaviors of zebrafish larvae were examined for their usefulness in screening for recessive defects in the visual system. The optokinetic response can be reliably and rapidly detected in 5-day larvae, whereas the phototactic response of larvae is variable and not robust enough to be useful for screening. We therefore measured optokinetic responses of mutagenized larvae as a genetic screen for visual system defects. Third-generation larvae, representing 266 mutagenized genomes, were examined for abnormal optokinetic responses. Eighteen optokinetic-defective mutants were identified and two mutants that did not show obvious morphological defects, no optokinetic response a (noa) and partial optokinetic response a (poa), were studied further. We recorded the electroretinogram (ERG) to determine whether these two mutations affect the retina. The b-wave of noa larvae was grossly abnormal, being delayed in onset and significantly reduced in amplitude. In contrast, the ERG waveform of poa larvae was normal, although the b-wave was reduced in amplitude in bright light. Histologically, the retinas of noa and poa larvae appeared normal. We conclude that noa larvae have a functional defect in the outer retina, whereas the outer retina of poa larvae is likely to be normal. 相似文献
80.
Catalytic mechanism of the adenylyl and guanylyl cyclases: Modeling and mutational analysis
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Yu Liu Arnold E. Ruoho Vibha D. Rao James H. Hurley 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(25):13414-13419
The adenylyl and guanylyl cyclases catalyze the formation of 3′,5′-cyclic adenosine or guanosine monophosphate from the corresponding nucleoside 5′-triphosphate. The guanylyl cyclases, the mammalian adenylyl cyclases, and their microbial homologues function as pairs of homologous catalytic domains. The crystal structure of the rat type II adenylyl cyclase C2 catalytic domain was used to model by homology a mammalian adenylyl cyclase C1-C2 domain pair, a homodimeric adenylyl cyclase of Dictyostelium discoideum, a heterodimeric soluble guanylyl cyclase, and a homodimeric membrane guanylyl cyclase. Mg2+ATP or Mg2+GTP were docked into the active sites based on known stereochemical constraints on their conformation. The models are consistent with the activities of seven active-site mutants. Asp-310 and Glu-432 of type I adenylyl cyclase coordinate a Mg2+ ion. The D310S and D310A mutants have 10-fold reduced Vmax and altered [Mg2+] dependence. The NTP purine moieties bind in mostly hydrophobic pockets. Specificity is conferred by a Lys and an Asp in adenylyl cyclase, and a Glu, an Arg, and a Cys in guanylyl cyclase. The models predict that an Asp from one domain is a general base in the reaction, and that the transition state is stabilized by a conserved Asn-Arg pair on the other domain. 相似文献